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. 2025 Jun 5.
doi: 10.14309/ajg.0000000000003573. Online ahead of print.

Effectiveness and Safety of Advanced Combination Treatment in Patients With Refractory Inflammatory Bowel Disease or Concomitant Immune-Mediated Disease or Extraintestinal Manifestations: A Multicenter Canadian Study

Virginia Solitano  1   2   3 , Ropo Ebenezer Ogunsakin  1 , Yuhong Yuan  1 , Charles N Bernstein  4 , Talat Bessissow  5 , Brian Bressler  6 , Frank Hoentjen  7 , Lisa van Lierop  7 , Yvette Leung  8 , Christopher Ma  9 , John Kenneth Marshall  10 , Neeraj Narula  10 , Mohammed Alahmari  10 , Jeffrey D Mccurdy  11 , Sanjay Murthy  11 , Remo Panaccione  9 , Greg Rosenfeld  8 , Raquel Milgrom  12 , Mark Silverberg  12 , Vipul Jairath  1   3
Affiliations

Effectiveness and Safety of Advanced Combination Treatment in Patients With Refractory Inflammatory Bowel Disease or Concomitant Immune-Mediated Disease or Extraintestinal Manifestations: A Multicenter Canadian Study

Virginia Solitano et al. Am J Gastroenterol. .

Abstract

Introduction: Owing to the therapeutic ceiling associated with inflammatory bowel disease (IBD) therapies, some patients may require 2 advanced therapeutic agents, known as advanced combination treatment (ACT) to control disease or treat associated extraintestinal manifestations (EIMs).

Methods: We included adult patients with IBD from 9 Canadian centers treated with either 2 biological therapies, a biological plus an oral small molecule, or 2 small molecules. Indications for ACT were the following: (i) refractory IBD, (ii) uncontrolled immune mediated diseases, and (iii) uncontrolled EIMs. Primary outcomes were cumulative rates of clinical and endoscopic response and remission at 6 and 12 months. Secondary outcomes included serious adverse events and infections. Cox-proportional hazard analyses identified independent predictors of treatment effectiveness.

Results: We included 105 IBD patients (76 Crohn's disease, 29 ulcerative colitis) with median age 35 years (Interquartile Range 35.4-40.8). At baseline, 39% had perianal involvement, 58% had failed at least 3 advanced therapies, and 40% had previous surgery. The primary reason for ACT was refractory IBD (63.8%), with the add-on approach used in 97.1% cases. The most frequent combination was antitumor necrosis factor + anti-integrin. At 12 months, cumulative rates of clinical and endoscopic response were 60.0% and 32.4%, respectively, and remission rates were 29.5% and 28.6%. Perianal disease was associated with reduced clinical remission (hazard ratio [HR] = 0.33, 95% confidence interval [CI]: 0.17-0.65, P = 0.001) and endoscopic response (HR = 0.42, 95% CI: 0.12-0.50, P = 0.001). Longer disease duration (HR = 0.96, 95% CI: 0.92-0.99, P = 0.035) and baseline steroid use (HR = 0.39, P = 0.006) was associated with reduced clinical remission. Serious adverse events and infections occurred in 12.4% and 7.6% of patients, respectively.

Discussion: ACT was effective in achieving clinical and endoscopic outcomes in patients with refractory IBD or concomitant immune-mediated diseases/EIMs, with favorable safety profile.

Keywords: Crohn's disease; combination; dual therapy; risk-benefit; ulcerative colitis.

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